Telomerase: A Dual Role in Cancer Progression and Aging-Related Diseases
Telomerase: A Dual Role in Cancer Progression and Aging-Related Diseases
Mansooreh Afshari,1,*Mohsen Sheykhhasan,2
1. Department of Biology, Semnan University, Semnan, Iran 2. Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran,
Introduction: Telomerase is a vital enzyme responsible for maintaining telomeres, the protective caps at the ends of chromosomes, which are crucial for cellular longevity and organismal survival. Telomere length serves as an indicator of cellular aging, as telomeres shorten with each cell division. This reduction in length has been strongly linked to age-related diseases such as cardiovascular disease, neurodegenerative disorders, and immune system decline.
In most normal somatic cells, telomerase is either inactive or minimally active, limiting the number of cell divisions, a process known as the Hayflick limit. Once cells reach this limit, they enter senescence or undergo programmed cell death. In cancer cells, however, telomerase regulation is disrupted. Many cancer cells reactivate telomerase, enabling them to bypass the Hayflick limit and proliferate indefinitely. This ability to manipulate telomerase is a key reason for cancer cells’ unchecked growth.
Studies suggest that cancer and aging share overlapping molecular pathways, reinforcing the connection between the two. Both processes involve DNA damage, oxidative stress, and cellular senescence. These shared mechanisms make telomerase a promising target for therapies addressing both cancer and age-related diseases.
Methods: This review is based on a thorough search of scientific literature from databases like PubMed, Scopus, ScienceDirect, and Google Scholar. Studies on telomerase function in cancer and aging were included, with particular emphasis on telomerase activation in cancer cells, its inhibition as a potential cancer treatment, and its role in combating age-related diseases.
Results: Studies show that telomerase is reactivated in around 85–90% of malignant tumors, making it an attractive target for cancer therapy. Inhibiting telomerase in cancer cells has been linked to reduced tumor growth, increased apoptosis (cell death), and delayed tumor progression. Telomerase reverse transcriptase (TERT), the enzyme's catalytic subunit, is key to telomerase activity. Overexpression of TERT is common in cancer cells, and its inhibition has been identified as a promising therapeutic approach.
Recent advancements in gene-editing technologies, particularly CRISPR/Cas9, have enabled the precise targeting of telomerase in cancer cells. CRISPR/Cas9 studies that disrupt the TERT gene have shown significant reductions in cancer cell viability, both in laboratory settings and in living organisms. This suggests that targeting TERT could slow cancer progression and improve treatment outcomes.
Conversely, telomerase deficiency has severe consequences for aging. Telomerase-deficient mice exhibit accelerated aging symptoms, such as hair loss, impaired tissue regeneration, and shortened lifespan. This indicates that telomerase activation might hold therapeutic potential for treating age-related conditions by restoring telomere function and possibly slowing cellular aging.
A crucial aspect of telomere function is the shelterin complex, a group of proteins that protects telomeres and prevents them from being mistaken for damaged DNA. Mutations in shelterin proteins can lead to genomic instability and increase cancer risk. Research suggests that correcting these mutations could improve stem cell function, extend lifespan, and reduce cancer susceptibility.
Balancing telomerase inhibition and stimulation presents a promising therapeutic strategy. Inhibiting telomerase in cancer cells could limit tumor growth, while stimulating telomerase in normal cells may extend lifespan, particularly in those with telomere-related disorders. These dual roles underscore telomerase's importance as a key target for future medical treatments.
Conclusion: Aging and cancer are closely linked through shared molecular pathways, especially those involving telomerase and telomere maintenance. Inhibiting telomerase in cancer cells shows promise as a cancer treatment, while activating telomerase in normal cells could extend lifespan and treat age-related diseases. As research continues, telomerase is likely to become a central focus for therapies addressing both aging and cancer, with significant implications for future medicine.